Antibodies to Malaria Vaccine Candidates Pvs25 and Pvs28 Completely Block the Ability ofPlasmodium vivaxTo Infect Mosquitoes

Abstract

Transmission-blocking vaccines are one strategy for controlling malaria, whereby sexual-stage parasites are inhibited from infecting mosquitoes by human antibodies. To evaluate whether the recently cloned Plasmodium vivax proteins Pvs25 and Pvs28 are candidates for a transmission-blocking vaccine, the molecules were expressed in yeast as secreted recombinant proteins. Mice vaccinated with these proteins adsorbed to aluminum hydroxide developed strong antibody responses against the immunogens, although for Pvs28, this response was genetically restricted. Antisera against both recombinant Pvs25 and Pvs28 recognized the corresponding molecules expressed by cultured sexual-stage parasites isolated from patients with P. vivax malaria. The development of malaria parasites in mosquitoes was completely inhibited when these antisera were ingested with the infected blood meal. Pvs25 and Pvs28, expressed in Saccharomyces cerevisiae, are as yet the only fully characterized transmission-blocking vaccine candidates against P. vivax that induce such a potent antiparasite response.

Human Host-Derived Cytokines Associated with Plasmodium vivax Transmission from Acute Malaria Patients to Anopheles darlingi Mosquitoes in the Peruvian Amazon

“…[1][2][3][4][5] A variety of determinants modulate transmission, including gametocyte quality, vector competence, and human innate and acquired immunity. Although host antibodies [6][7][8] have been shown to affect parasite infectivity for mosquitoes, transmission inefficiency is still observed in malaria hypoendemic regions where presence of antibody is thought to be low. 2,9 Previous work in Sri Lanka has suggested that humoral factors associated with the malarial paroxism reduces parasite infectivity for mosquitoes.…”

In Vitro Generation of Plasmodium falciparum Ookinetes

“…1 Interest in the potential of transmission-blocking vaccines to control or even eradicate malaria has recently increased; such vaccines work by inducing antibodies against components of the parasite's sexual stage forms, hence reducing infectivity of the reservoir, humans, for the obligate vector, Anopheles mosquitoes. [2][3][4][5][6][7][8][9][10][11] More detailed understanding of Plasmodium falciparum transmission stage biology, particularly ookinetes, would directly contribute to human transmission-blocking vaccine development.…”

Transgenesis, Paratransgenesis and Transmission Blocking Vaccines to Prevent Insect-Borne Diseases

“…vivax sexual stage surface proteins, orthologs of P. falciparum TBV candidates, also have been isolated and tested in transmission blocking experiments. Pvs25, a Pfs25 ortholog, is expressed on the surfaces of the insect-stages, zygotes and mature ookinetes, whereas Pvs28, a Pfs28 ortholog, is mainly expressed on retorts and mature ookinetes (Hisaeda et al 2000).…”

“…P. falciparum proteins Pfs25, Pfs28, Pfs48/45, and Pfs230, and their orthologs in Plasmodium vivax, have been tested in transmission-blocking assays (Quakyi et al 1987;Kaslow et al 1988;Duffy & Kaslow 1997;Hisaeda et al 2000;Sattabongkot et al 2003;Malkin et al 2005;Outchkourov et al 2008). …”